The absorption of a drug as it passes through the alimentary canal can be controlled by coating the pharmaceutical with a substance which will at certain pH values retard release of the drug while at other pH values promote disintegration and/or leaching of the drug from the dosage form. For example, a coat comprised of an anionic polymer such as cellulose acetate phthalate prevents premature disintegration of the pharmaceutical in the acidic environment of the stomach and promotes rapid release of the drug in the intestine. Such a coat is commonly called an enteric coat (e.g., see U.S. Pat. No. 4,857,337 for a description of enteric coated aspirin dosage forms).
The enteric coat surrounds the core dosage form with a film which is hydrophobic at acidic pH values. At pH values below 4, the monolayers of the film are arranged in a compact alignment resistant to penetration by water and ions. However, at pH values of 5.8 and more basic the monolayers expand allowing the penetration of water and ions.
The enteric coat is applied by coating the pharmaceutical dosage form with a liquid enteric coating mixture in the presence of a sufficient amount of heat to vaporize the solvents. The mixture usually contains, in addition to an anionic polymer, a plasticizer or a combination of plasticizers. The plasticizers cross-link the polymer molecules together by hydrogen bonding which results in a lattice structure that adds tensile strength to the esoteric coat and promotes adhesion to the surface of the dosage form. The enteric coat can contain other ingredients such as surfactants, pigments, and fillers.
Organic solvents or aqueous mixtures of organic solvents are often used to prepare the enteric coating mixtures (e.g., see U.S. Pat. No. 4,377,568 for a description of aqueous alcoholic enteric coating dispersions). However, organic solvents have to be recycled and can result in contamination of the enteric coat. When water is used to prepare an enteric coating dispersion, a detackifier and glidant (e.g., talc) may be needed to avoid sticking or clumping of the pharmaceutical dosage forms during the application process. Constant and vigorous stirring is usually required to prevent the anionic detachifier/glidant from settling out. Because of the stirring, foaming may occur and antifoam agents may be necessary.
The solubility of an anionic polymer in an aqueous solvent can be increased by adding base (e.g., see Japanese Kokai No. J5 9193-382-A for a description of an aqueous enteric coating solution of carboxymethylethyl cellulose and base). However, the free base that is present in the solvent will also then be present in the resulting enteric coat and the capacity of the coat to resist disintegration in an acidic environment is reduced.
In addition to the various process-related problems which can occur during the application of the enteric coat, other problems may become apparent after the coat has dried (e.g., see Rowe, R. C. (1981) J Pharm Pharmacol 33: 423). A sufficient amount of enteric coating material must be applied to the uncoated dosage form to assure the formation of an adequate enteric coat. However, as the amount of the enteric coating material is increased, problems may occur as a result of the internal stress that develops in the coat as it dries. For example, a common problem associated with enteric coated tablets is logo-bridging (i.e., the enteric coat pulls away from a tablet surface and the legibility of the monogram is lost). Typically, logo-bridging occurs when the weight gain due to the enteric coat exceeds 2-3% of the uncoated tablet weight.
The disclosure of the above and other documents referred to throughout this application are incorporated herein by reference.